9-cis beta-carotene Inhibits Atherosclerosis Development in Female LDLR-/- Mice

Background: Several epidemiological studies have shown that diets rich in carotenoids are associated with reduced risk for cardiovascular disease. However, administration of synthetic all-trans beta-carotene was reported to have no effect on cardiovascular disease. We previously demonstrated that the 9-cis beta-carotene-rich powder of the alga Dunaliella bardawil inhibits atherogenesis and reduces plasma non-HDL cholesterol levels in mice. Context and purpose of this study: We sought to investigate whether isolated 9-cis beta-carotene inhibits atherogenesis in a murine model of atherosclerosis. Results: Twelve-week-old female LDL receptor knockout mice (LDLR-/-) were pretreated for 2 weeks with regular chow diet fortified with the alga Dunaliella powder, 9-cis beta-carotene isomer, all-trans beta-carotene isomer, or 9-cis retinoic acid, followed by 10 weeks of a high-fat diet with the same fortifications. In contrast to Dunaliella, 9-cis beta-carotene did not inhibit the high fat diet-induced elevation of plasma cholesterol. Additionally, diet fortification with Dunaliella powder, beta-carotene isomers, or 9-cis retinoic acid did not change the plasma retinol or retinoic acid levels. Nevertheless, 9-cis beta-carotene significantly inhibited atherogenesis compared to the control mice (39% reduction). Conclusions: The results suggest that 9-cis beta-carotene should be considered as an anti-atherogenic agent in the human diet.